[Molecular mechanism underlying differentiation of HL-60 cells induced by hexamethylene bisacetamide].
The objective of this study was to investigate the effect of hexamethylene bisacetamide (HMBA) on differentiation of HL-60 cells and its possible molecular mechanism. HL-60 cells were co-cultured with different concentrations of HMBA (0.5, 1, 2 mmol/L) for 4 days, then the proliferation was assayed by MTT at different time points. Wright-Giemsa staining was used to observe the change in morphology. Cell differentiation antigen CD11b expression and the altered distribution of cell cycle in HL-60 induced by HMBA were analyzed by flow cytometry. The expressions of c-myc, mad1, p21, p27, hTERT and HDAC1 mRNA were detected by RT-PCR. The results indicated that the proliferation of HL-60 cells was inhibited by HMBA in a time-and-dose-dependent manner. Upon 2 mmol/L HMBA treatment, the HL-60 cells arrested at G(0)/G(1) phase and differentiated into granular line in morphology, with the up-regulation of CD11b expression. The expression of c-myc and hTERT mRNA obviously down-regulated, the expression of p21, p27 and mad1 mRNA up-regulated, while there was no change of the expression of hTERT mRNA. It is concluded that effect of HMBA on the differentiation of HL-60 cells may partly contribute to switch from c-myc to mad1 expression, to up-regulate expressions of p21 and p27 mRNA, and down-regulate hTERT mRNA expression, while there is no relation with the expression of HDAC1 mRNA.
Ren
Xia
X
Institute of Basic Medical Sciences, Shandong Academy of Medical Sciences, Jinan 250062, Shangdong Province, China.
Wen
Pei-E
PE
Yang
Wei-Hua
WH
Tang
Tian-Hua
TH
Ren
Hai-Quan
HQ
Zhang
Zhi-Yong
ZY
Zhao
Hai-Tao
HT
Fan
Hua
H
Qiao
Gao-Juan
GJ
Jiang
Guo-Heng
GH
D000081:Acetamides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans
D000081:Acetamides; D000970:Antineoplastic Agents; C014026:hexamethylene bisacetamide